Binquan Luan, Ruhong Zhou
Nature Communications
Currently, the new coronavirus disease 2019 (COVID-19) is a global pandemic without any well-calibrated treatment. To inactivate the SARS-CoV-2 virus that causes COVID-19, the main protease (Mpro) that performs key biological functions in the virus has been the focus of extensive studies. With the fast-response experimental efforts, the crystal structures of Mpro of the SARS-CoV-2 virus have just become available recently. Herein, we theoretically investigated the mechanism of binding between the Mpro's pocket and various marketed drug molecules being tested in clinics to fight COVID-19 that show promising outcomes. By combining the existing experimental results with our computational ones, we revealed an important ligand binding mechanism of the Mpro, demonstrating that the binding stability of a ligand inside the Mpro pocket can be significantly improved if part of the ligand occupies its so-called "anchor"site. Along with the highly potent drugs and/or molecules (such as nelfinavir) revealed in this study, the newly discovered binding mechanism paves the way for further optimizations and designs of Mpro's inhibitors with a high binding affinity.
Binquan Luan, Ruhong Zhou
Nature Communications
Xiaochuan Ma, Sangyun Lee, et al.
Nanotoxicology
Binquan Luan, Marcelo A. Kuroda
ACS Nano
Binquan Luan, Tien Huynh, et al.
Journal of Physical Chemistry B